Contemporary update of cancer control after radical prostatectomy in the UK

Despite a significant increase of the number of radical prostatectomies (RPs) to treat organ-confined prostate cancer, there is very limited documentation of its oncological outcome in the UK. Pathological stage distribution and changes of outcome have not been audited on a consistent basis. We present the results of a multicentre review of postoperative predictive variables and prostatic-specific antigen (PSA) recurrence after RP for clinically organ-confined disease. In all, 854 patient's notes were audited for staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. Median follow-up was 52 months for the remaining 705 patients. The median PSA was 10 ng ml−1. A large migration towards lower PSA and stage was seen. This translated into improved PSA survival rates. Overall Kaplan–Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probability for PSA ranges 20 ng ml−1 was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P<0.0001). PSA recurrence-free survival probabilities for pathological Gleason grade 2–4, 5 and 6, 7 and 8–10 at 5 years were 0.84, 0.66, 0.55 and 0.21, respectively (log rank, P<0.0001). Similarly, 5-year PSA recurrence-free survival probabilities for pathological stages T2a, T2b, T3a, T3b and T4 were 0.82, 0.78, 0.48, 0.23 and 0.12, respectively (log rank, P=0.0012). Oncological outcome after RP has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic compared to quoted survival figures in the literature. Survival figures based on pathological stage and Gleason grade may serve to counsel patients postoperatively and to stratify patients better for adjuvant treatment

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig

LHRH agonists in prostate cancer:frequency of treatment, serum testosterone measurement and castrate level: consensus opinion from a roundtable discussion

Background: Options for lowering testosterone in patients with prostate cancer include bilateral orchiectomy, oestrogens and luteinising hormone-releasing hormone (LHRH) agonists. LHRH agonists have become widely used in the treatment of prostate cancer. Roundtable assembly: In May 2006, a team of experts convened a roundtable assembly to discuss key issues associated with the use of LHRH agonists in the treatment of prostate cancer. Roundtable discussion: The discussion centred on the frequency of treatment with LHRH agonists, the role of serum testosterone (ST) measurement as part of routine follow-up, and the recommended castrate level of ST. Several formulations of LHRH agonists are available, including 3-month depots that coincide with visit frequency for prostate-specific antigen (PSA) testing. Appropriate monitoring of patients receiving LHRH agonists continues to be based on PSA levels. ST determination is not recommended as part of routine follow-up, and does not provide additional prognostic benefit or improved overall management for the majority of patients. However, determination of ST may be useful in selected patients, such as those with rising PSA levels or in cases where there is doubt over LHRH agonist administration or absorption. Achieving levels of ST similar to those obtained after orchiectomy is important for patient outcomes, although there is no evidence that a lower ST level (<50 ng/dl) results in additional clinical benefits. Conclusions: LHRH agonists should be considered first-choice testosterone-lowering therapy for the treatment of prostate cancer, with the 3-month depot formulation providing optimal convenience and flexibility. Assessment of patients receiving LHRH agonists should be based on PSA levels rather than ST levels, although levels of ST similar to those obtained after orchiectomy still need to be achieved. Further studies are warranted before the potential therapeutic benefit of considerably lowered ST levels can be fully assessed